Method for preparing immunomodulator for dairy cow in later perinatal period by using pyrroloquinoline quinine disodium salt and application of pyrroloquinoline quinine disodium salt

By using pyrroloquinoline quinone disodium salt (PQQ) as an immunomodulator in the postpartum period of dairy cows, the problem of decreased immunity in the postpartum period of dairy cows was solved, the immunoglobulin content and anti-inflammatory factor level of dairy cows were increased, and postpartum recovery and metabolic regulation were promoted.

CN121818642APending Publication Date: 2026-04-10INNER MONGOLIA UNIV FOR THE NATITIES
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Patent Information

Application Number
CN202610058256.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-01-16
Publication Date
2026-04-10

AI Technical Summary

Technical Problem

Dairy cows experience a decline in immunity during the peripartum period, leading to high morbidity and reduced productivity. Existing technologies struggle to effectively regulate postpartum metabolism and increase immunoglobulin levels in dairy cows.

Method used

Pyrroloquinoline quinone disodium salt (PQQ) was used as an immunomodulator for dairy cows and added to the basal diet during the postpartum period at a dose of 20 mg/day for 21 consecutive days to regulate the level of immune factors in the blood of dairy cows.

Benefits of technology

It significantly increases the levels of immunoglobulins A, G, and M in the blood of dairy cows, reduces the levels of pro-inflammatory factors, promotes postpartum stress recovery in dairy cows, prevents diseases, and regulates metabolic pathways such as phospholipid, fatty acid, bile acid, pyrimidine, and amino acid metabolism.

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Abstract

The invention discloses a method for using pyrroloquinoline quinone disodium salt to prepare a dairy cow immunity regulating agent in the later perinatal period and application of the pyrroloquinoline quinone disodium salt in the later perinatal period of the dairy cow, and relates to the technical field of dairy cow breeding, and the key points of the technical scheme are as follows: the pyrroloquinoline quinone disodium salt is used as an effective component of the dairy cow immunity regulating agent in the later perinatal period of the dairy cow; the usage amount of the pyrroloquinoline quinine disodium salt is 20 mg / day, the pyrroloquinoline quinine disodium salt is added into the basic ration of the dairy cow every day according to the amount of 20 mg per day, and the dairy cow is continuously fed with the pyrroloquinoline quinine disodium salt for 21 days. The pyrroloquinoline quinone disodium salt is used as the immunomodulator in the later perinatal period of the dairy cow, can regulate postpartum metabolism of the dairy cow, improve the content of immune globulin and the level of anti-inflammatory factors in blood of the dairy cow, reduce the levels of proinflammatory factors, tumor necrosis factors alpha and interferon gamma in the blood, and contribute to promoting postpartum stress recovery of the dairy cow and preventing diseases.
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Description

TECHNICAL FIELD

[0001] The present application relates to the field of dairy cow breeding, more particularly, it relates to a method for preparing an immune regulator for dairy cows in the postpartum period and application thereof. BACKGROUND

[0002] Dairy cow intensive farming is a modern farming mode that improves production efficiency through high-density feeding, standardized management and application of advanced technology. Intensive farming can effectively promote the improvement of dairy cow breeds, the preparation of feed and the standardization of milking equipment, and accelerate the modernization process of the dairy industry.

[0003] Intensive farming greatly improves the production efficiency of dairy cows, but at the same time, it also causes a series of effects on the physiological and metabolic activities of dairy cows. For example, high-yield dairy cows are often in a high-stress state during calving and lactation, and a large amount of active oxygen (ROS) produced in the body causes the oxidative stress index (OSI) to rise, causing the immune capacity of dairy cows in the postpartum period to decrease, the incidence to increase, and the lactation and reproductive performance of dairy cows to decrease. SUMMARY

[0004] The purpose of the present application is to provide a method for preparing an immune regulator for dairy cows in the postpartum period and application thereof, and pyrroloquinoline quinone disodium salt is used as an immune regulator for dairy cows, which aims to regulate postpartum metabolism of dairy cows, increase the content of immunoglobulin in the blood of dairy cows and the level of anti-inflammatory factors, and reduce the levels of pro-inflammatory factors, tumor necrosis factor alpha and interferon gamma in the blood, which helps to promote the recovery of postpartum stress, anti-inflammatory and disease prevention of dairy cows.

[0005] The above technical purpose of the present application is achieved by the following technical scheme: an immune regulator for dairy cows, characterized in that: the effective component of the immune regulator for dairy cows is pyrroloquinoline quinone disodium salt (Pyrroloquinolinequinone disodium salt, PQQ), the purity of the pyrroloquinoline quinone disodium salt is more than 99%, and the use amount of the pyrroloquinoline quinone disodium salt is 20 mg / day.

[0006] The present application further provides a method for using the immune regulator for dairy cows, which adds the immune regulator for dairy cows to the basic daily ration of dairy cows in the postpartum period, adds an amount of 20 mg per day, and continuously feeds for 21 days.

[0007] The present application further provides:

[0008] The base ration is formulated as follows: whole plant corn silage 58.03%, alfalfa hay 6.19%, soybean hulls 3.09%, beet pellet meal 3.09%, steam pressed corn 2.58%, corn meal 11.73%, bran 1.54%, soybean meal 6.17%, cottonseed meal 5.23%, sodium bicarbonate 0.56%, magnesium oxide 0.24%, premix 1.54%.

[0009] The application further provides a use of pyrroloquinoline quinone disodium salt in preparation of an immune regulation agent for a dairy cow in a perinatal period.

[0010] In summary, the application has the following beneficial effects:

[0011] After pyrroloquinoline quinone disodium salt is used as an immune regulation agent for a dairy cow in a perinatal period, the content of immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) in the blood of the dairy cow can be significantly improved, the levels of interleukin-4 (IL-4), nitric oxide (NO) and inducible nitric oxide synthase (INOS) can be improved, and the levels of interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) can be reduced.

[0012] The results of non-targeted omics detection of the metabolites in the blood plasma of the dairy cow by liquid chromatography-mass spectrometry (LC-MS) show that PQQ significantly up-regulates 46 kinds of metabolites (such as nebularine, arabinosyladenosine, xanthopterin, cinobufotalin, 4-methylstyrene, austenol, cycloheptatrienone A, phosphatidylcholine (18:3(9Z,12Z,15Z) / 20:0), beta-hypoglycemic factor, santalwood spirit, polyethylene glycol monooleate N4, eicosapentaenoic acid ethyl ester, hepcidin and ascorbic acid, etc. Figure 1 and Figure 2 significantly down-regulates 74 kinds of metabolites (such as tryptophan-glycine, dynorphin B (6-9), lysophosphatidic acid (0:0 / 18:2(9Z,12Z)), glycerophosphocholine (17:2 / 3:0), 2-amino-1-butanol and platelet activating factor, etc. Figure 1 and Figure 2 According to KEGG alignment, they are respectively involved in animal body phospholipid metabolism, fatty acid metabolism, bile acid metabolism, pyrimidine metabolism, amino acid metabolism and regulation of neurotransmitter synthesis and release pathways. Figure 3

[0013] In summary, the addition of PQQ in the dairy cow diet in a perinatal period helps to regulate the postpartum metabolism of the dairy cow, improve the content of immunoglobulin in the blood of the dairy cow and the level of anti-inflammatory factors, reduce the level of pro-inflammatory factors, tumor necrosis factor alpha and interferon gamma in the blood, and help to promote the postpartum stress recovery of the dairy cow and prevent diseases. BRIEF DESCRIPTION OF DRAWINGS​

[0014] Figure 1 is a volcano plot of differential metabolites in blood of dairy cows caused by PQQ in embodiments of the present application;

[0015] Figure 2 is a typical differential metabolite in blood of dairy cows caused by PQQ in embodiments of the present application;

[0016] Figure 3 are 20 important metabolic pathways related to differential metabolites in blood of dairy cows in embodiments of the present application. DETAILED DESCRIPTION

[0017] The following description is in conjunction with the accompanying drawings Figures 1-3 The present application is further described in detail.

[0018] Embodiments

[0019] 20 mg PQQ was added to the basal diet of dairy cows in the peripartum period (formula see Table 1, nutritional level see Table 2) for 21 days.

[0020] Table 1 Formula of basal diet

[0021]

[0022] Note: * Mineral premix (dry matter basis): vitamin A 300 KIU / kg, vitamin D 70 KIU / kg, vitamin E 2000 IU / kg, biotin 40 mg / kg, zinc 2560 mg / kg, copper 600 mg / kg; manganese 1160 mg / kg, selenium 12 mg / kg, iodine 40 mg / kg, cobalt 12 mg / kg, calcium 13-20%, phosphorus 2-5%, sodium oxide 15-17%, magnesium 4-8%.

[0023] Table 2 Nutritional level of basal diet

[0024]

[0025] Note: * Net energy for lactation was calculated according to NRC (2001), and other nutritional levels were measured values.

[0026] Table 3 Effect of 20 mg PQQ added to the diet on immune indicators in blood of dairy cows in the peripartum period

[0027]

[0028] Note: Different superscripts in the table indicate significant differences (P <0.05).

[0029] As shown in Table 3, after 21 days of feeding with the diet added with PQQ, the levels of immunoglobulin IgA, IgG and IgM in the blood of the perinatal dairy cows were significantly improved, which was helpful to improve the recognition and neutralization ability of the organism to the pathogen. Meanwhile, the contents of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in the blood were significantly improved, which was helpful to inhibit the growth and reproduction of the pathogen and remove abnormal cells. On the other hand, the level of anti-inflammatory cytokine IL-4 was significantly improved, and the levels of pro-inflammatory cytokines IL-1β, IL-2, IL-6, tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) were reduced, which exhibited a significant anti-inflammatory effect.

[0030] The specific embodiments are only an explanation of the present application, which is not a limitation of the present application. Those skilled in the art can make modifications to the embodiments without creative contribution after reading the specification, as long as the modifications are within the scope of the claims of the present application.

Claims

1. An immunomodulatory agent for dairy cows in the postpartum period, characterized by: The active ingredient of the peripartum immunomodulator for dairy cows is disodium pyrroloquinoline quinone, with the molecular formula C. 14 H4N2Na2O8, the purity of the disodium pyrroloquinoline quinone is above 99%, and the usage of the disodium pyrroloquinoline quinone is 20 mg / day.

2. The method of using the peripartum immunomodulator for dairy cows according to claim 1, characterized in that: The peripartum immune regulator was added to the daily basal diet of peripartum dairy cows at a dose of 20 mg per day for 21 consecutive days.

3. The method of using the peripartum immunomodulator for dairy cows according to claim 1, characterized in that: The formulation of the basal diet is as follows: Whole-plant corn silage: 58.03%, alfalfa hay: 6.19%, soybean hulls: 3.09%, beet kernel meal: 3.09%, steam-flaked corn: 2.58%, corn flour: 11.73%, wheat bran: 1.54%, soybean meal: 6.17%, cottonseed meal: 5.23%, baking soda: 0.56%, magnesium oxide: 0.24%, premix: 1.54%.

4. The use of pyrroloquinoline quinone disodium salt in the preparation of the peripartum immunomodulator for dairy cows as described in claim 1.